The present invention relates to the estimation of action potential, and in particular action potential duration, of muscle tissues. More particularly it relates to a novel sensor designed for the chronic estimation of the local action potential duration, using close bipolar technique, in particular for cardiac purposes.
The cardiac muscle is made of excitable tissue that can generate action potentials spontaneously or as a result of a stimulus. The electric potential invokes a mechanical response in the form of a contraction of the muscle tissue.
A single muscle twitch is characterized by a short period during which tension is being developedxe2x80x94the contraction phase. This is followed by a relaxation phase during which the muscle returns to a resting condition.
The following account refers to the heart muscle in order to better explain the action potential mechanism.
Myocardial activation normally begins with the spontaneous sodium calcium dependent depolarization of cells within the sinoatrial (SA) node located approximately at the junction of the right atrium and superior vena cava. The impulse then propagates in a wave-like fashion through the myocardium to the atrioventricular (AV) node located in the lower portion of the interatrial septum. Conducting through the AV node primarily involves the calcium-dependent process of depolarization and is delayed owing to membrane properties of the nodal cells.
The impulse is rapidly transmitted through the bundle of His, which then bifurcates into fibers The distal portion of the specialized conducting system is a network of smaller fibers, which delivers the propagated impulse to the non-specialized ventricular tissue, resulting in a synchronized myocardial contraction. The action potential of the bundle of His-Purkinje system and ventricular myocardium has five typical phases. In its resting state, the interior of most cardiac cells, with the exception of the sinus and AV nodes is approximately 80 to 90 mV negative with respect to a reference extracellular electrode. The resting membrane potential is primarily determined by the concentration gradient of potassium across the cell membrane. The concentration of intracellular potassium is approximately 30 times greater than its extracellular concentration, and it is the diffusion of this ion out of the cell that results in the resting transmembrane potential of approximately xe2x88x9290 mV in the fully repolarized state. The extracellular sodium concentration is approximately 15 times greater than its extracellular concentration, and the rapid influx of this ion into the cells results in the usual process of rapid cellular depolarization. The sodium channels rapidly inactivate and do not reactivate until the membrane potential is repolarized to less then xe2x88x9250 mV. A slower depolarization process may occur that predominantly involves calcium ions. The ionic species responsible for the action potential vary among the cardiac tissues, and the configuration of the action potential is therefore unique to each tissue.
The resting phase lasts until the cell is activated (phase 0). When an activation signal reaches the cell, the cell membrane is locally depolarized. If the depolarization reaches a certain threshold value, the cell membrane will rapidly depolarize within a few msec to a value of approximately 20 mV. The cell then rapidly partially repolarizes and the signal is reduced in about 10 mV, followed by further slow repolarization reducing the signal further by about 20 mV over a period of about 300 msec. The slower part of depolarization is called the plateau phase. The repolarization phases of the transmembrane action potential comprise phases 1-3. During the plateau period, the contraction of the muscle occurs. Finally, the cell reaches the resting membrane potential (phase 4).
Refractoriness is a property of the cells that defines the period of recovery that cells require before they can respond again to an excitation by a stimulus after being discharged. The absolute refractory period (ARP) is defined by the part of the action potential during which no stimulus, regardless of its strength, can evoke another response. The effective refractory period (ERP) is that part of the action potential where a stimulus can only evoke a local non-propagated response. The relative refractive period (RRP) extends from the end of the ERP to the instant in time when the tissue is fully recovered. During the RRP, a stimulus greater than the threshold strength is required to evoke a response which is propagated slowly in respect to the normal propagation. After the completion of the action potential cycle, excitability recovers and evokes responses that have characteristics similar to the spontaneous normal response.
Characteristics of the action potential in the heart muscle cells such as action potential duration, its amplitude or information regarding the refractory periods is of significant relevance. Online measurements of the action potential duration may allow monitoring the progress of a severe illness of the heart caused by cardiomyopathy. Moreover, it may be efficient in detecting and predicting the occurrence of arrhytmic events. Action potential duration measurements serve in the determination of the tissue viability, detection of eschemic changes, determination of drug effects, and monitoring effects of induced signals, such as pacing, deffibrilation, electrical tissue control. Attention is drawn to PCT Patent Application No. PCT/IL97/00012, published as WO 97/25098, which disclosed a method and apparatus for locally controlling the electrical and/or mechanical activity of cardiac muscle cells, in situ. Preferably a continuous control is applied, but alternatively, discrete application is possible too. Chronical action potential measurements in situ have the advantage of providing crucial information for the determination of the working parameters of the electrical muscle control administered in accordance with the above mentioned patent application, and in particular serve as a feedback channel to determine the efficiency of the administered control. The data obtained through action potential duration measurements can be also processed by the microprocessor of the apparatus described in the above mentioned patent application, and be used to determine the parameters of the induced electrical signal issued to the muscle by the apparatus its timing and sequence. It may also be used for safety considerations, to initiate the halting of any further electrical signal induction, upon identifying substantial changes in the localized refractory period.
The measurement of the global Q-T interval, from body ECG, provides an unreliable estimate of action potential duration, from the onset of ventricular depolarization to the end of the T wave. Refractory periods, which are reflected in the duration of cardiac action potential, vary from one myocardial region to another, The Q-T interval, which approximates the duration of electrical systole, is known to vary from one cardiac area to another. In patients with prolonged Q-T intervals, the variation from one site to another is much higher than the variation in normal subjects (see, for example, xe2x80x9cSpatial Distribution of QT intervals: An alternative approach to QT dispersionxe2x80x9d, P. Van Leeuwen et al., PACE, Vol. 19, 1996, P. 1894-94, xe2x80x9cRelation of human cardiac action potential duration to the interval between beats: implications for the validity of rate corrected QT interval (QTc)xe2x80x9d, W. A. Seed et al., Br Heart Journals 1987, 57, 32-7, and xe2x80x9cMonophasic action potential mapping in human subjects with normal electrocardiograms: direct evidence for the genesis of the T wavexe2x80x9d, M. R. Franz et al., Circulation, Vol. 75, No. 2, 1987, 379-386).
Conventional bipolar and unipolar leads cannot be used to study the spatial and temporal sequences of localized repolarization. Prior art bipolar leads used in ECG fail to record sharp spikes typical of rapidly propagating excitation front. The typical drawbacks are summed up as follows; the measured signal is obtained over a very large area between two relatively distant locations (practically over the entire heart), polarization following the pulse prevents real measurement, the actual surface area of the conventional electrodes is too large, and consequently the resolution of the reading is relatively low.
A method for measuring in-vivo action potential, called monophasic action potential (MAP), was developed (see, for example U.S. Pat. No. 4,682,603 (Franz), filed Mar. 6, 1984, U.S. Pat. No, 4,955,382 (Franz et al.), filed Apr. 3, 1989, and U.S. Pat. No. 4,979,510 (Franz et al.), filed Jul. 27, 1988). MAP directly records the waveform of the beating heart from two separate electrodes MAP recordings had been obtained in humans from atrial and ventricular endocardial and epicardial sites. The disadvantage of this method is the short circuiting effect of damaged cells, which prevents the signal from advancing, and the relatively large number of cells in contact with the suction electrode, reduces the accuracy as it refers to a summation of the signal propagating over a large number of cells. Moreover, the use of plunge electrodes, suction electrodes and pressure contact electrodes, may induce the formation of scar tissue or connective tissue in the area connecting the electrode tip to the tissue. Furthermore it be chronically used, as after a short period of time the tissue becomes numb and looses its viability Therefore, this device is not suitable for intramural sites or for continuous or chronic recordings (over a long period of time). It should be also noted that MAP is an active measurement, which involves interefering actively with the natural activity of the cardiac tissue, and this can inflict bias on the results.
Some of the theories and experimental evidence on the use of monophasic action potential methods are disclosed in detail in Patent Application titled xe2x80x9cApparatus and Methods for Chronic Measurement of Monophasic Action Potentialxe2x80x9d, Pat. No. 6,152,882.
It is an object of the present invention to provide a sensor for the measurement of the action potential duration possessing the ability to estimate action potential duration and consequently the refractory periods in chronic situation in-vivo with high degree of accuracy.
It is another object of the present invention to provide a sensor for the measurement of the action potential duration which allows local measurement over a small number of tissue cells.
Yet another object of the present invention is to provide such a sensor for measurement of the action potential duration which allows continuous recordings.
It is another object of the present invention to provide such a sensor for the measurement of action potential duration which does not interfere with the natural activity of the cardiac tissue, and is employed passively.
An aspect of the present invention is the deployment of a bipolar electrode over a localized region of a muscle tissue, covering a small number of tissue cells.
It is therefore provided, in accordance with a preferred embodiment of the present invention, a bipolar sensor for a muscle action potential measurement comprising two electrodes, exposed at the distal end of an electrode lead, wherein said electrodes at said distal end are kept at a very close proximity, wherein the cross-section of said electrodes detection surface is very small, and wherein said sensor is electrically connected to an electrical reading device circuitry.
Furthermore, in accordance with another preferred embodiment of the present invention, the distance between said electrodes at the distal end of said lead is not more than 7 mm, and preferably not more than 2 mm.
Furthermore, in accordance with another preferred embodiment of the present invention, each of the two electrodes has detection surface area in the range of 0.1 and 3.0 mm sqr.
Furthermore, in accordance with another preferred embodiment of the present invention, the electrodes have substantially the same detecting surface area.
Furthermore, in accordance with another preferred embodiment of the present invention, the electrodes are separated by an electrically insulating material.
Furthermore, in accordance with another preferred embodiment of the present invention, the processing means is a part of an electrical tissue control system, and the data retrieved by the sensor is used to identify the length of the refractory period, and wherein the processing means determines, by applying a predetermined algorithm, the possible need for a change in the signals induced by said electrical tissue control system.
There is further provided, in accordance with another preferred embodiment of the present invention, a sensor for the measurement of action potential duration of muscle tissue, said sensor comprising two electrodes exposed at the distal end of an electrode lead, said electrodes surrounded by a guard-ring electrode, for screening noise or background signals, wherein said electrodes at said distal end are kept at a very close proximity, and wherein said sensor is electrically connected to a processing means for processing the signal detected by the sensor.
There is further provided, in accordance with another preferred embodiment of the present invention, a sensor for the measurement of action potential duration of muscle tissue, said sensor comprising two electrodes coaxially positioned at the distal end of an electrode lead, wherein said electrodes at said distal end are kept at a very close proximity, and wherein said sensor is electrically connected to a processing means for processing the signal detected by the sensor.
There is further provided, in accordance with another preferred embodiment of the present invention, a sensor for the measurement of action potential duration of muscle tissue, said sensor comprising two electrodes positioned at a side wall of an electrode lead, wherein said electrodes are kept at a very close proximity, and wherein said sensor is electrically connected to a processing means for processing the signal detected by the sensor.
There is further provided, in accordance with another preferred embodiment of the present invention, a sensor for the measurement of action potential duration of muscle tissue, said sensor comprising two electrodes positioned at a side wall of an electrode lead, confined by a pair of guard-ring electrodes, positioned at either sides of the two sensing electrodes, along the lead, and serve as guard rings, wherein said two electrodes are kept at a very close proximity, and wherein said sensor is electrically connected to a processing means for processing the signal detected by the sensor.
Furthermore, in accordance with another preferred embodiment of the present invention, the guard-ring electrodes are kept at equal potential.
And finally, in accordance with another preferred embodiment of the present invention, the processing means comprise two parallely electrically connected amplifiers, a low-band pass amplifier, said low-band pass amplifier having a frequency response optimally tuned to pass the repolarizarion signal, and a high-band pass amplifier, said high-band pass amplifier having a frequency response optimally tuned to pass the depolarization signal, wherein said amplifiers are parallely electrically connected to an analog-to-digital filter, and wherein said analog-to-digital filter""s output is electrically connected to a microporcessor unit.